title: Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome.
abstract: Sjögren's syndrome is a common autoimmune disease (affecting ∼0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjögren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10(-114)), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 × 10(-19)), STAT4 (Pmeta = 6.80 × 10(-15)), IL12A (Pmeta = 1.17 × 10(-10)), FAM167A-BLK (Pmeta = 4.97 × 10(-10)), DDX6-CXCR5 (Pmeta = 1.10 × 10(-8)) and TNIP1 (Pmeta = 3.30 × 10(-8)). We also observed suggestive associations (Pmeta < 5 × 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjögren's syndrome.
authors.affiliation: 1] Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. [2] Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Christopher J
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authors.lastname: Radfar
authors.forename: Michael D
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authors.lastname: Rohrer
authors.forename: Donald U
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authors.lastname: Stone
authors.forename: Jonathan D
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authors.lastname: Wren
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Patrick M
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authors.lastname: Gaffney
authors.forename: Judith A
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authors.lastname: James
authors.forename: Roald
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authors.lastname: Omdal
authors.forename: Marie
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authors.lastname: Wahren-Herlenius
authors.forename: Gabor G
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authors.lastname: Illei
authors.forename: Torsten
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authors.lastname: Witte
authors.forename: Roland
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authors.lastname: Jonsson
authors.forename: Maureen
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authors.lastname: Rischmueller
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authors.lastname: Rönnblom
authors.forename: Gunnel
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authors.lastname: Nordmark
authors.forename: Wan-Fai
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authors.lastname: Ng
authors.forename: Xavier
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authors.lastname: Mariette
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Anaya
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Rhodus
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Segal
authors.forename: R Hal
authors.initials: RH
authors.lastname: Scofield
authors.forename: Courtney G
authors.initials: CG
authors.lastname: Montgomery
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authors.lastname: Harley
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Sivils
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics*; D014644:Genetic Variation; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II